Ginsenoside Rk3 Regulates Nonalcoholic Steatohepatitis by Modulation of Intestinal Flora and the PI3K/AKT Signaling Pathway in C57BL/6 Mice.

Abstract

Non-alcoholic steatohepatitis (NASH) has become the most important reason of liver disease around the world and is predisposed to further progression to cirrhosis and hepatocellular carcinoma. Ginsenoside Rk3 has been reported to have a plenty of biological activities, including anti-apoptotic, anti-anemia, and protective effects against acute kidney injury. However, whether ginsenoside Rk3 can improve NASH has not been reported yet. Therefore, the purpose of this study is to investigate the protective effect of ginsenoside Rk3 against NASH and its mechanism of action. C57BL/6 mice were treated with different dosages of ginsenoside Rk3 after being established as a NASH model. Our results showed that Rk3 administration significantly improved liver inflammation, lipid deposition, and fibrosis caused by a high-fat-high-cholesterol (HFHC) diet and CCl4 injection in mice. Notably, ginsenoside Rk3 was discovered significantly to inhibit the PI3K/AKT signaling pathway. Additionally, treatment with ginsenoside Rk3 remarkably amended the abundance of short-chain fatty acids. These changes were associated with beneficial variations to the variety and composition of the intestinal microbiota. In conclusion, ginsenoside Rk3 ameliorates hepatic non-alcoholic lipid inflammation and triggers changes in the beneficial intestinal flora, helping to reveal host-microbe interactions. The outcomes of this study indicate that ginsenoside Rk3 is a promising drug candidate for the treatment of NASH.

• Authors: Mengdi Guo, Chenhui Zhu, Rongzhan Fu, Xiaoxuan Ma, Zhiguang Duan, Daidi Fan
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 71 Issue 24 Pg. 9370-9380 (Jun 21 2023) ISSN: 1520-5118 [Electronic] United States
• PMID: 37288986 (Publication Type: Journal Article)

Chemical References

• Proto-Oncogene Proteins c-akt
• ginsenoside Rk3
• Phosphatidylinositol 3-Kinases
• Lipids

Topics

• Mice
• Animals
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Gastrointestinal Microbiome
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Mice, Inbred C57BL
• Signal Transduction
• Inflammation (metabolism)
• Lipids (pharmacology)
• Liver (metabolism)
• Diet, High-Fat (adverse effects)
• Disease Models, Animal